This proposal request support for the purchase of al Leica TCS SP confocal microscope. This microscope, which will be a shared resource, will be crucial for the ongoing research of investigators working in several departments at NYUMC. The projects of the major users are focused on analyzing cell-cell interactions and intracellular signaling pathways and require precise localization of proteins or cellular constituents in cultured cells or complex tissues. Most projects are focused on cell-cell interactions in the developing nervous system. These include studies of: i) the regulation of neuromuscular synapse formation in genetically modified mice and the mechanisms that regulate clustering of postsynaptic proteins (Burden), ii) the signaling pathways that regulate gliogenesis by co- localizing signaling components in cultured cells (Chao, Salzer) and analyzing glial development in genetically modified mice (Chao), iii) the cell adhesion molecules and other signals that regulate the posteriorly- directed outgrowth of specific GFP expressing neurons in C. elegans (Clark) and motor fibers at the exit junction in Drosophila (Sink), and iv) the mechanisms that regulate differentiation of developing neurons in the mammalian central nervous system (Fishell). A second area of research, which is concerned with host cell/parasite interactions, studies the mechanisms by which Shigella and Salmonella lead t macrophage apoptosis via activation of ICE-dependent pathways (Zychlinsky). The ability to precisely localize proteins to specific cellular compartments and to infer protein intera9tions by co-localization will be crucial to an understanding of the pathogenetic and signal transduction mechanisms. The above projects are being undertaken by senior and recently recruited faculty members, who will cooperate in supporting and operating this confocal facility. The enhanced resolution and sensitivity of this microscope, as well as its ability to effectively image thicker tissue, will be crucial to the success of these projects.